Simulated microgravity increases beta-adrenergic lipolysis in human adipose tissue.
The effect of a sustained decrease in sympathetic nervous activity, achieved through 5-day head-down bed rest (HDBR), on the beta-adrenergic lipolytic activity of s.c. adipose tissue was studied in eight healthy men. The in situ beta-adrenoceptor (AR) sensitivity was studied using the microdialysis method. Local perfusion of increasing concentrations of isoprenaline showed an increased beta-AR sensitivity to lipolysis (assessed by extracellular glycerol concentration) and to vascular tone (assessed by the ethanol clearance). The adrenergic sensitivity of isolated adipocytes was studied in vitro. Basal lipolysis and the response to nonselective (isoprenaline) or selective (dobutamine, terbutaline, and CGP 12177) beta-AR agonists were increased after HDBR as was the lipolytic effect of dibutyryl cAMP. When data were expressed as a percentage of the dibutyryl cAMP effect to rule out the postreceptor events, basal and lipolytic responses to beta-AR agonists where similar before and during HDBR. The alpha 2-AR-mediated antilipolytic effects of adrenaline were not modified. Lymphocyte beta-AR number was unchanged during HDBR. Our results demonstrate that a sustained sympathoinhibition induces an increase in the lipolytic beta-adrenergic response in adipose tissue and suggest that this hypersensitization is linked to an increase in the postreceptor steps of the lipolytic cascade in the adipocyte rather than to changes in beta-adrenoceptors.
Barbe
P
P
Institut National de la Santé et de la Recherche Médicale U-317, Laboratoire de Pharmacologie Médicale et Clinique, Toulouse, France.
Galitzky
J
J
De Glisezinski
I
I
Riviere
D
D
Thalamas
C
C
Senard
J M
JM
Crampes
F
F
Lafontan
M
M
Berlan
M
M
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000318:Adrenergic beta-Agonists; D000328:Adult; D003994:Bucladesine / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005990:Glycerol / Q000378:metabolism; D018475:Head-Down Tilt; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis; D008297:Male; D017551:Microdialysis; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013726:Terbutaline / Q000494:pharmacology; D014893:Weightlessness
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; D003994:Bucladesine; D007545:Isoproterenol; D013726:Terbutaline; D005990:Glycerol; C033394:CGP 12177; D004837:Epinephrine